Cellular virus-specific immune responses are important host defenses, and are likely to control the initial burst of HIV-1 replication following acute infection. Although a vigorous MHC class I restricted cytotoxic T lymphocyte (CTL) response has been detected in HIV-1 infection, viral replication persists, leading to the progressive depletion of CD4+ T lymphocytes in the majority of cases. The factors which allow disease progression in the face of this immune response are poorly understood. Possible explanations include the loss of responding CTL to apoptosis or clonal exhaustion, or HIV-1 sequence variation leading to immune escape. In each of these cases, the failure to generate new CTL may relate in part to defects in antigen presentation. The bone marrow-derived dendritic cell (DC) is a professional antigen presenting cell (APC) which plays a central role in the generation of primary immune responses. In addition, DC pulsed with HIV-1 peptide have been shown to induce CTL responses in vitro and in vivo. Despite this, little is known of the quantitative and qualitative differences in the ability of DC from HIV-1 seronegative and seropositive individuals to induce these CTL responses, or of the ability of DC to generate or expand CTL responses in HIV-1 infected individuals are varying stages of disease progression. DC derived from previously identified HLA A2.1 positive individuals with early or late stage HIV-1 infection will be pulsed with an immunodominant p17-gag derived epitope, or one of two reverse transcriptase (RT) derived epitopes, and the ability to generate CTL responses will be compared to that of DC derived from HLA 2.1, HIV-1 negative positive persons. In addition, Influenza and hepatitis C virus (HCV) derived epitopes will be included as controls. The CTL generated will then be characterized by T cell receptor (TCR) sequence analysis to determine whether specific clonal responses in individuals with persistent or progressive disease use an increasingly diverse TCR repertoire. The functional ability of these in vitro derived CTL to inhibit HIV-1 replication will also be tested. These studies will provide important information regarding potential defects in antigen presentation in HIV-1 infection, and the role these defects may play in disease.